title: Voluntary exercise protects against methamphetamine-induced oxidative stress in brain microvasculature and disruption of the blood-brain barrier.
abstract: BACKGROUND
  There is no effective therapeutic intervention developed targeting cerebrovascular toxicity of drugs of abuse, including methamphetamine (METH). We hypothesize that exercise protects against METH-induced disruption of the blood-brain barrier (BBB) by enhancing the antioxidant capacity of cerebral microvessels and modulating caveolae-associated signaling. Mice were subjected to voluntary wheel running for 5 weeks resembling the voluntary pattern of human exercise, followed by injection with METH (10 mg/kg). The frequency, duration, and intensity of each running session were monitored for each mouse via a direct data link to a computer and the running data are analyzed by Clock lab™ Analysis software. Controls included mice sedentary that did not have access to running wheels and/or injections with saline.
  
  
  RESULTS
  METH induced oxidative stress in brain microvessels, resulting in up regulation of caveolae-associated NAD(P)H oxidase subunits, and phosphorylation of mitochondrial protein 66Shc. Treatment with METH disrupted also the expression and colocalization of tight junction proteins. Importantly, exercise markedly attenuated these effects and protected against METH-induced disruption of the BBB integrity.
  
  
  CONCLUSIONS
  The obtained results indicate that exercise is an important modifiable behavioral factor that can protect against METH-induced cerebrovascular toxicity. These findings may provide new strategies in preventing the toxicity of drug of abuse.
authors.forename: Michal
authors.initials: M
authors.lastname: Toborek
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Seelbach
authors.forename: Cetewayo S
authors.initials: CS
authors.lastname: Rashid
authors.forename: Ibolya E
authors.initials: IE
authors.lastname: András
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Minseon
authors.initials: M
authors.lastname: Park
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Esser
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D055806:Microvessels / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine